There is a growing body of information that viruses play a vital role in a broad range of diseases, some of which represent the most serious of man's ills. Arthritis, juvenile arthritis, diabetes, Hodgkin's disease and various immunological diseases and degenerative diseases of the central nervous system have been linked to viruses as the causative agents.
At present, the control of virus infections is primarily achieved by means of immunization vaccines. For example, poliomyelitis, smallpox, measles and influenza are well recognized diseases in which viral vaccines have proven effective. In general, however, viral vaccines have had only a moderate success in animal prophylaxis. Each vaccine acts primarily against a specific virus and is not heterophilic in the protection it offers. Hence, vaccines do not provide a practical solution against the wide array of infectious viruses, even where limited, as for example, solely to respiratory viruses.
One approach to the control of virus-related diseases and, particularly to the spread of such virus diseases, has been to search for medicinal agents or chemotherapeutic agents which are capable of inhibiting the growth of viruses, thereby preventing the spread of disease as well as preventing further damage to cells and tissues of the animal host which have not as yet been infected. Heretofore, only a limited number of virus infections such as smallpox, Asian influenza and herpes keratitis have been susceptible to prevention by chemical antiviral agents. Sulfonamides and antibiotics which have revolutionized the treatment of bacterial infections have substantially no effect upon virus infections. Certain infections caused by large viruses, such as lymphogranuloma venereum, psittacosis and trachoma have been successfully treated using antibiotics and sulfa drugs. However, the majority of infections have not been responsive to attack by chemotherapeutic agents. Thus, it can be seen that there is a need for new chemotherapeutic agents which are effective against a broad range of virus diseases, and which at the same time, are non-toxic to the host.
As a result of a long series of investigations, applicants have discovered a novel class of antiviral agents which are bis-basic ether derivatives of 9-substituted phenanthrene and which also include their corresponding 10-oxa and 10-aza derivatives. A more descriptive designation for these compounds in accordance with Chemical Abstracts nomenclature would be to describe them as bis-basic ether derivatives of 9-phenanthrol, 6(5H)-phenanthridinone and 6H-dibenzo[b,d]pyran-6-one. These compounds are effective against a wide spectrum of viral infections and are useful in treating such infections either prophylactically or therapeutically.
U.S. Pat. No. 3,592,819 is the closest art known to applicants and discloses certain bis-basic ethers and thioethers of various substituted fluorenes, 9-fluorenols and 9-fluorenones useful as antiviral agents. Certain of the bis-basic ethers described therein serve as starting materials for the preparation of some of the compounds of the present invention.
The bis-basic ethers described and claimed herein, however, are derived from a totally different and chemically unrelated 6,6,6 tricyclic aromatic ring system which differs substantially from the fluorene nucleus. To applicants' knowledge the compounds described and claimed herein are novel compounds which have not been previously described nor reported in the literature. Additionally, applicants are unaware of any previously reported bis-basic derivatives of 9-phenanthrol, 6(5H)-phenanthridinone or 6H-dibenzo[b,d]pyran-6-one which possess antiviral activity. The compounds described herein possess a wide spectrum of antiviral activity in varying degrees which could not have been predicted from a knowledge of the present state of the art.